tbuckley/cabot-search huggingface dataset:
Optical Coherence Tomography–Guided versus Angiography-Guided PCI
Authors: Ziad A. Ali, Ulf Landmesser, Akiko Maehara, Mitsuaki Matsumura, Richard A. Shlofmitz, Giulio Guagliumi, Matthew J. Price, Jonathan M. Hill, Takashi Akasaka, Francesco Prati, Hiram G. Bezerra, William Wijns, David Leistner, Paolo Canova, Fernando Alfonso, Franco Fabbiocchi, Ozgen Dogan, Robert J. McGreevy, Robert W. McNutt, Hong Nie, Jana Buccola, Nick E.J. West, Gregg W. Stone
Journal: New England Journal of Medicine (2023)

Data regarding clinical outcomes after optical coherence tomography (OCT)–guided percutaneous coronary intervention (PCI) as compared with angiography-guided PCI are limited. Download a PDF of the Research Summary. In this prospective, randomized, single-blind trial, we randomly assigned patients with medication-treated diabetes or complex coronary-artery lesions to undergo OCT-guided PCI or angiography-guided PCI. A final blinded OCT procedure was performed in patients in the angiography group. The two primary efficacy end points were the minimum stent area after PCI as assessed with OCT and target-vessel failure at 2 years, defined as a composite of death from cardiac causes, target-vessel myocardial infarction, or ischemia-driven target-vessel revascularization. Safety was also assessed. The trial was conducted at 80 sites in 18 countries. A total of 2487 patients underwent randomization: 1233 patients were assigned to undergo OCT-guided PCI, and 1254 to undergo angiography-guided PCI. The minimum stent area after PCI was 5.72±2.04 mm2 in the OCT group and 5.36±1.87 mm2 in the angiography group (mean difference, 0.36 mm2; 95% confidence interval [CI], 0.21 to 0.51; P<0.001). Target-vessel failure within 2 years occurred in 88 patients in the OCT group and in 99 patients in the angiography group (Kaplan–Meier estimates, 7.4% and 8.2%, respectively; hazard ratio, 0.90; 95% CI, 0.67 to 1.19; P=0.45). OCT-related adverse events occurred in 1 patient in the OCT group and in 2 patients in the angiography group. Stent thrombosis within 2 years occurred in 6 patients (0.5%) in the OCT group and in 17 patients (1.4%) in the angiography group. Among patients undergoing PCI, OCT guidance resulted in a larger minimum stent area than angiography guidance, but there was no apparent between-group difference in the percentage of patients with target-vessel failure at 2 years. (Funded by Abbott; ILUMIEN IV: OPTIMAL PCI ClinicalTrials.gov number, NCT03507777.) QUICK TAKE VIDEO SUMMARYOCT-Guided vs. Angiography-Guided PCI 02:10
Clinical Outcomes with GLP-1 Receptor Agonists in Patients with Heart Failure: A Systematic Review and Meta-analysis of Randomized Controlled Trials
Authors: Huilei Zhao, Yang Liu, Menglu Liu, Yi Xu, Qin Ling, Weichun Lin, Jing Zhang, Zhiwei Yan, Jianyong Ma, Weiguang Li, Yujie Zhao, Peng Yu, Xiao Liu, Jingfeng Wang
Journal: Drugs (2023)
Substance Use Disorder Program Availability in Safety-Net and Non–Safety-Net Hospitals in the US
Authors: Ji E. Chang, Berkeley Franz, José A. Pagán, Zoe Lindenfeld, Cory E. Cronin
Journal: JAMA Network Open (2023)

Importance Safety-net hospitals (SNHs) are ideal sites to deliver addiction treatment to patients with substance use disorders (SUDs), but the availability of these services within SNHs nationwide remains unknown. Objective To examine differences in the delivery of different SUD programs in SNHs vs non-SNHs across the US and to determine whether these differences are increased in certain types of SNHs depending on ownership. Design, Setting, and Participants This cross-sectional analysis used data from the 2021 American Hospital Association Annual Survey of Hospitals to examine the associations of safety-net status and ownership with the availability of SUD services at acute care hospitals in the US. Data analysis was performed from January to March 2022. Main Outcomes and Measures This study used 2 survey questions from the American Hospital Association survey to determine the delivery of 5 hospital-based SUD services: screening, consultation, inpatient treatment services, outpatient treatment services, and medications for opioid use disorder (MOUD). Results A total of 2846 hospitals were included: 409 were SNHs and 2437 were non-SNHs. The lowest proportion of hospitals reported offering inpatient treatment services (791 hospitals [27%]), followed by MOUD (1055 hospitals [37%]), and outpatient treatment services (1087 hospitals [38%]). The majority of hospitals reported offering consultation (1704 hospitals [60%]) and screening (2240 hospitals [79%]). In multivariable models, SNHs were significantly less likely to offer SUD services across all 5 categories of services (screening odds ratio [OR], 0.62 [95% CI, 0.48-0.76]; consultation OR, 0.62 [95% CI, 0.47-0.83]; inpatient services OR, 0.73 [95% CI, 0.55-0.97]; outpatient services OR, 0.76 [95% CI, 0.59-0.99]; MOUD OR, 0.6 [95% CI, 0.46-0.78]). With the exception of MOUD, public or for-profit SNHs did not differ significantly from their non-SNH counterparts. However, nonprofit SNHs were significantly less likely to offer all 5 SUD services compared with their non-SNH counterparts (screening OR, 0.52 [95% CI, 0.41-0.66]; consultation OR, 0.56 [95% CI, 0.44-0.73]; inpatient services OR, 0.45 [95% CI, 0.33-0.61]; outpatient services OR, 0.58 [95% CI, 0.44-0.76]; MOUD OR, 0.61 [95% CI, 0.46-0.79]). Conclusions and Relevance In this cross-sectional study of SNHs and non-SNHs, SNHs had significantly lower odds of offering the full range of SUD services. These findings add to a growing body of research suggesting that SNHs may face additional barriers to offering SUD programs. Further research is needed to understand these barriers and to identify strategies that support the adoption of evidence-based SUD programs in SNH settings.
Trends in Suicide Rates Among Post-9/11 US Military Veterans With and Without Traumatic Brain Injury From 2006-2020
Authors: Jeffrey T. Howard, Ian J. Stewart, Megan E. Amuan, Jud C. Janak, Krista J. Howard, Mary Jo Pugh
Journal: JAMA Neurology (2023)

This cohort study examines trends in suicide rates for veterans with and without traumatic brain injury compared with the US adult population.
MicroRNA137-loaded lipid nanoparticles regulate synaptic proteins in the prefrontal cortex
Authors: Michelle C. Palumbo, Milan Gautam, Alex Sonneborn, Kilsun Kim, Phillip A. Wilmarth, Ashok P. Reddy, Xiao Shi, Daniel L. Marks, Gaurav Sahay, Atheir I. Abbas, Aaron Janowsky
Journal: Molecular Therapy (2023)
Sarah C. Kalser, Ph.D.Obituary
Authors: Jay H. Hoofnagle
Journal: Hepatology (2023)

Liver Diseases Research Branch, Division of Digestive Diseases and Nutrition, National Institute of Diabetes and Digestive and Kidney Diseases National Institutes of Health, Bethesda, Maryland, USAEmail: [email protected] Abbreviations: NIDDK, National Institute of Diabetes and Digestive and Kidney Diseases; NIH, National Institutes of Health.
Genome-Wide Association Study Identifies Pharmacogenomic Variants Associated With Metformin Glycemic Response in African American Patients With Type 2 Diabetes
Authors: Baojun Wu, Sook Wah Yee, Shujie Xiao, Fei Xu, Sneha B. Sridhar, Mao Yang, Samantha Hochstadt, Whitney Cabral, David E. Lanfear, Monique M. Hedderson, Kathleen M. Giacomini, L. Keoki Williams
Journal: Diabetes Care (2023)

OBJECTIVE Metformin is the most common treatment for type 2 diabetes (T2D). However, there have been no pharmacogenomic studies for T2D in which a population of color was used in the discovery analysis. This study sought to identify genomic variants associated with metformin response in African American patients with diabetes. RESEARCH DESIGN AND METHODS Patients in the discovery set were adult, African American participants from the Diabetes Multi-omic Investigation of Drug Response (DIAMOND), a cohort study of patients with T2D from a health system serving southeast Michigan. DIAMOND participants had genome-wide genotype data and longitudinal electronic records of laboratory results and medication fills. The genome-wide discovery analysis identified polymorphisms correlated to changes in glycated hemoglobin (HbA1c) levels among individuals on metformin monotherapy. Lead associations were assessed for replication in an independent cohort of African American participants from Kaiser Permanente Northern California (KPNC) and in European American participants from DIAMOND. RESULTS The discovery set consisted of 447 African American participants, whereas the replication sets included 353 African American KPNC participants and 466 European American DIAMOND participants. The primary analysis identified a variant, rs143276236, in the gene ARFGEF3, which met the threshold for genome-wide significance, replicated in KPNC African Americans, and was still significant in the meta-analysis (P = 1.17 × 10−9). None of the significant discovery variants replicated in European Americans DIAMOND participants. CONCLUSIONS We identified a novel and biologically plausible genetic variant associated with a change in HbA1c levels among African American patients on metformin monotherapy. These results highlight the importance of diversity in pharmacogenomic studies.
Biochemical Recurrence Surrogacy for Clinical Outcomes After Radiotherapy for Adenocarcinoma of the Prostate
Authors: Soumyajit Roy, Tahmineh Romero, Jeff M. Michalski, Felix Y. Feng, Jason A. Efstathiou, Colleen A.F. Lawton, Michel Bolla, Philippe Maingon, Theo de Reijke, David Joseph, Wee Loon Ong, Matthew R. Sydes, David P. Dearnaley, Alison C. Tree, Nathalie Carrier, Abdenour Nabid, Luis Souhami, Luca Incrocci, Wilma D. Heemsbergen, Floris J. Pos, Almudena Zapatero, Araceli Guerrero, Ana Alvarez, Carmen Gonzalez San-Segundo, Xavier Maldonado, Robert E. Reiter, Matthew B. Rettig, Nicholas G. Nickols, Michael L. Steinberg, Luca F. Valle, T. Martin Ma, Matthew J. Farrell, Beth K. Neilsen, Jesus E. Juarez, Jie Deng, Sitaram Vangala, Norbert Avril, Angela Y. Jia, Nicholas G. Zaorsky, Yilun Sun, Daniel Spratt, Amar U. Kishan
Journal: Journal of Clinical Oncology (2023)

The surrogacy of biochemical recurrence (BCR) for overall survival (OS) in localized prostate cancer remains controversial. Herein, we evaluate the surrogacy of BCR using different surrogacy analytic methods.Individual patient data from 11 trials evaluating radiotherapy dose escalation, androgen deprivation therapy (ADT) use, and ADT prolongation were obtained. Surrogate candidacy was assessed using the Prentice criteria (including landmark analyses) and the two-stage meta-analytic approach (estimating Kendall's tau and the R2). Biochemical recurrence-free survival (BCRFS, time from random assignment to BCR or any death) and time to BCR (TTBCR, time from random assignment to BCR or cancer-specific deaths censoring for noncancer-related deaths) were assessed.Overall, 10,741 patients were included. Dose escalation, addition of short-term ADT, and prolongation of ADT duration significantly improved BCR (hazard ratio [HR], 0.71 [95% CI, 0.63 to 0.79]; HR, 0.53 [95% CI, 0.48 to 0.59]; and HR, 0.54 [95% CI, 0.48 to 0.61], respectively). Adding short-term ADT (HR, 0.91 [95% CI, 0.84 to 0.99]) and prolonging ADT (HR, 0.86 [95% CI, 0.78 to 0.94]) significantly improved OS, whereas dose escalation did not (HR, 0.98 [95% CI, 0.87 to 1.11]). BCR at 48 months was associated with inferior OS in all three groups (HR, 2.46 [95% CI, 2.08 to 2.92]; HR, 1.51 [95% CI, 1.35 to 1.70]; and HR, 2.31 [95% CI, 2.04 to 2.61], respectively). However, after adjusting for BCR at 48 months, there was no significant treatment effect on OS (HR, 1.10 [95% CI, 0.96 to 1.27]; HR, 0.96 [95% CI, 0.87 to 1.06] and 1.00 [95% CI, 0.90 to 1.12], respectively). The patient-level correlation (Kendall's tau) for BCRFS and OS ranged between 0.59 and 0.69, and that for TTBCR and OS ranged between 0.23 and 0.41. The R2 values for trial-level correlation of the treatment effect on BCRFS and TTBCR with that on OS were 0.563 and 0.160, respectively.BCRFS and TTBCR are prognostic but failed to satisfy all surrogacy criteria. Strength of correlation was greater when noncancer-related deaths were considered events.
A fresh start for IVM: capacitating the oocyte for development using pre-IVM
Authors: Robert B Gilchrist, Tuong M Ho, Michel De Vos, Flor Sanchez, Sergio Romero, William L Ledger, Ellen Anckaert, Lan N Vuong, Johan Smitz
Journal: Human Reproduction Update (2023)

While oocyte IVM is practiced sporadically it has not achieved widespread clinical practice globally. However, recently there have been some seminal advances in our understanding of basic aspects of oocyte biology and ovulation from animal studies that have led to novel approaches to IVM. A significant recent advance in IVM technology is the use of biphasic IVM approaches. These involve the collection of immature oocytes from small antral follicles from minimally stimulated patients/animals (without hCG-priming) and an ∼24 h pre-culture of oocytes in an advanced culture system ('pre-IVM') prior to IVM, followed by routine IVF procedures. If safe and efficacious, this novel procedure may stand to make a significant impact on human ART practices.
Duration of Type 2 Diabetes and Incidence of Cancer: An Observational Study in England
Authors: Francesco Zaccardi, Suping Ling, Karen Brown, Melanie Davies, Kamlesh Khunti
Journal: Diabetes Care (2023)

OBJECTIVE To investigate the association between duration of type 2 diabetes and cancer incidence. RESEARCH DESIGN AND METHODS In the Clinical Practice Research Datalink database, we identified 130,764 individuals with type 2 diabetes aged ≥35 years at diagnosis who were linked to hospital and mortality records. We used sex-stratified Royston–Parmar models with two timescales to estimate incidence rates of all cancers, the four commonest cancers in the U.K. (colorectal, lung, prostate, breast), and the obesity-related cancers (e.g., liver, ovary) between 1 January 1998 and 14 January 2019, by age and diabetes duration. RESULTS During 1,089,923 person-years, 18,977 incident cancers occurred. At the same age, rates of all cancers in men and women did not vary across durations ranging from diagnosis to 20 years; conversely, for any duration, there was a strong, positive association between age and cancer rates. In men, the rate ratio (95% CI) comparing 20 with 5 years of duration was 1.18 (0.82–1.69) at 60 years of age and 0.90 (0.75–1.08) at 80 years; corresponding ratios in women were 1.07 (0.71–1.63) and 0.84 (0.66–1.05). This pattern was observed also for the four commonest cancers. For obesity-related cancers, although rates were generally higher in individuals with a higher BMI, there was no association with duration at any level of BMI. CONCLUSIONS In this study, we did not find evidence of an association between duration of type 2 diabetes and risk of cancer, with the higher risk observed for longer durations related to ageing.
Survival of Patients With Cancer With <i>DPYD</i> Variant Alleles and Dose-Individualized Fluoropyrimidine Therapy—A Matched-Pair Analysis
Authors: Jonathan E. Knikman, Tycho A. Wilting, Marta Lopez-Yurda, Linda M. Henricks, Carin A.T.C. Lunenburg, Femke M. de Man, Didier Meulendijks, Peter Nieboer, Helga J. Droogendijk, Geert-Jan Creemers, Caroline M.P.W. Mandigers, Alexander L.T. Imholz, Ron H.J. Mathijssen, Johanneke E.A. Portielje, Liselot Valkenburg-van Iersel, Annelie Vulink, Marlene H.W. van der Poel, Arnold Baars, Jesse J. Swen, Hans Gelderblom, Jan H.M. Schellens, Jos H. Beijnen, Henk-Jan Guchelaar, Annemieke Cats
Journal: Journal of Clinical Oncology (2023)

DPYD-guided fluoropyrimidine dosing improves patient safety in carriers of DPYD variant alleles. However, the impact on treatment outcome in these patients is largely unknown. Therefore, progression-free survival (PFS) and overall survival (OS) were compared between DPYD variant carriers treated with a reduced dose and DPYD wild-type controls receiving a full fluoropyrimidine dose in a retrospective matched-pair survival analysis.Data from a prospective multicenter study (ClinicalTrials.gov identifier: NCT02324452) in which DPYD variant carriers received a 25% (c.1236G>A and c.2846A>T) or 50% (DPYD*2A and c.1679T>G) reduced dose and data from DPYD variant carriers treated with a similarly reduced dose of fluoropyrimidines identified during routine clinical care were obtained. Each DPYD variant carrier was matched to three DPYD wild-type controls treated with a standard dose. Survival analyses were performed using Kaplan-Meier estimates and Cox regression.In total, 156 DPYD variant carriers and 775 DPYD wild-type controls were available for analysis. Sixty-one c.1236G>A, 25 DPYD*2A, 13 c.2846A>T, and-when pooled-93 DPYD variant carriers could each be matched to three unique DPYD wild-type controls. For pooled DPYD variant carriers, PFS (hazard ratio [HR], 1.23; 95% CI, 1.00 to 1.51; P = .053) and OS (HR, 0.95; 95% CI, 0.75 to 1.51; P = .698) were not negatively affected by DPYD-guided dose individualization. In the subgroup analyses, a shorter PFS (HR, 1.43; 95% CI, 1.10 to 1.86; P = .007) was found in c.1236G>A variant carriers, whereas no differences were found for DPYD*2A and c.2846A>T carriers.In this exploratory analysis, DPYD-guided fluoropyrimidine dosing does not negatively affect PFS and OS in pooled DPYD variant carriers. Close monitoring with early dose modifications based on toxicity is recommended, especially for c.1236G>A carriers receiving a reduced starting dose.
The Relationship Between Time-Varying Achieved HbA1c and Risk of Coronary Events Depends on Haptoglobin Phenotype Among White and Black ACCORD Participants
Authors: Leah E. Cahill, Rachel A. Warren, Allie S. Carew, Andrew P. Levy, Henry N. Ginsberg, John Sapp, Orit Lache, Eric B. Rimm
Journal: Diabetes Care (2023)

Intensive glycemic therapy reduced coronary artery disease (CAD) events among White participants in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) study with the haptoglobin (Hp)2-2 phenotype, while participants without the Hp2-2 phenotype had no CAD benefit. The association between achieved glycated hemoglobin (HbA1c) and CAD for each Hp phenotype remains unknown.Achieved HbA1c was similar in each phenotype throughout the study. Prospectively collected HbA1c data (categorized as <6.0%, 6.0-6.5%, 6.6-6.9%, or ≥8.0% compared with 7.0-7.9%) from the ACCORD study, updated every 4 months over a median of 4.7 years, were analyzed in relation to CAD in the Hp2-2 (n = 3,322) and non-Hp2-2 (n = 5,949) phenotypes separately overall, and within White (63%, 37% Hp2-2) and Black (19%, 26% Hp2-2) participants using Cox proportional hazards regression with time-varying covariables.Compared with HbA1c of 7.0-7.9%, having HbA1c ≥8.0% was associated with CAD risk among White (adjusted HR [aHR] 1.43, 95% CI 1.03-1.98) and Black (2.86, 1.09-7.51) participants with the Hp2-2 phenotype, but not when all Hp2-2 participants were combined overall (1.30, 0.99-1.70), and not among participants without the Hp2-2 phenotype. HbA1c <7.0% was not associated with a lower risk of CAD for any Hp phenotype.Achieving HbA1c >8.0% compared with 7.0-7.9% was consistently associated with incident CAD risk among White and Black ACCORD participants with the Hp2-2 phenotype, while no association was observed among participants without the Hp2-2 phenotype. We found no evidence that HbA1c concentration <7.0% prevents CAD in either Hp phenotype group.
HDV RNA assays: Performance characteristics, clinical utility, and challenges
Authors: Heiner Wedemeyer, Mitchell Leus, Thomas R. Battersby, Jeffrey Glenn, Emmanuel Gordien, Saleem Kamili, Hema Kapoor, Harald H. Kessler, Oliver Lenz, Marc Lütgehetmann, Tonya Mixson-Hayden, Christian O. Simon, Michael Thomson, Gabriel Westman, Veronica Miller, Norah Terrault, Pietro Lampertico
Journal: Hepatology (2023)

Coinfection with HBV and HDV results in hepatitis D, the most severe form of chronic viral hepatitis, frequently leading to liver decompensation and HCC. Pegylated interferon alpha, the only treatment option for chronic hepatitis D for many years, has limited efficacy. New treatments are in advanced clinical development, with one recent approval. Diagnosis and antiviral treatment response monitoring are based on detection and quantification of HDV RNA. However, the development of reliable HDV RNA assays is challenged by viral heterogeneity (at least 8 different genotypes and several subgenotypes), intrahost viral diversity, rapid viral evolution, and distinct secondary structure features of HDV RNA. Different RNA extraction methodologies, primer/probe design for nucleic acid tests, lack of automation, and overall dearth of standardization across testing laboratories contribute to substantial variability in performance characteristics of research-based and commercial HDV RNA assays. A World Health Organization (WHO) standard for HDV RNA, available for about 10 years, has been used by many laboratories to determine the limit of detection of their assays and facilitates comparisons of RNA levels across study centers. Here we review challenges for robust pan genotype HDV RNA quantification, discuss particular clinical needs and the importance of reliable HDV RNA quantification in the context of drug development and patient monitoring. We summarize distinct technical features and performance characteristics of available HDV RNA assays. Finally, we provide considerations for the use of HDV RNA assays in the context of drug development and patient monitoring.
Real-Time Computer-Aided Detection of Colorectal Neoplasia During Colonoscopy
Authors: Cesare Hassan, Marco Spadaccini, Yuichi Mori, Farid Foroutan, Antonio Facciorusso, Paraskevas Gkolfakis, Georgios Tziatzios, Konstantinos Triantafyllou, Giulio Antonelli, Kareem Khalaf, Tommy Rizkala, Per Olav Vandvik, Alessandro Fugazza, Emanuele Rondonotti, Jeremy R. Glissen-Brown, Shunsuke Kamba, Marcello Maida, Loredana Correale, Pradeep Bhandari, Rodrigo Jover, Prateek Sharma, Douglas K. Rex, Alessandro Repici
Journal: Annals of Internal Medicine (2023)

Artificial intelligence computer-aided detection (CADe) of colorectal neoplasia during colonoscopy may increase adenoma detection rates (ADRs) and reduce adenoma miss rates, but it may increase overdiagnosis and overtreatment of nonneoplastic polyps.